Comparative genomic analysis identifies potential adaptive variation in Mycoplasma ovipneumoniae.

Mycoplasma ovipneumoniae is associated with respiratory disease in wild and domestic Caprinae globally, with wide variation in disease outcomes within and between host species. To gain insight into phylogenetic structure and mechanisms of pathogenicity for this bacterial species, we compared M. ovipneumoniae genomes for 99 samples from 6 countries (Australia, Bosnia and Herzegovina, Brazil, China, France and USA) and 4 host species (domestic sheep, domestic goats, bighorn sheep and caribou). Core genome sequences of M. ovipneumoniae assemblies from domestic sheep and goats fell into two well-supported phylogenetic clades that are divergent enough to be considered different bacterial species, consistent with each of these two clades having an evolutionary origin in separate host species. Genome assemblies from bighorn sheep and caribou also fell within these two clades, indicating multiple spillover events, most commonly from domestic sheep. Pangenome analysis indicated a high percentage (91.4 %) of accessory genes (i.e. genes found only in a subset of assemblies) compared to core genes (i.e. genes found in all assemblies), potentially indicating a propensity for this pathogen to adapt to within-host conditions. In addition, many genes related to carbon metabolism, which is a virulence factor for Mycoplasmas, showed evidence for homologous recombination, a potential signature of adaptation. The presence or absence of annotated genes was very similar between sheep and goat clades, with only two annotated genes significantly clade-associated. However, three M. ovipneumoniae genome assemblies from asymptomatic caribou in Alaska formed a highly divergent subclade within the sheep clade that lacked 23 annotated genes compared to other assemblies, and many of these genes had functions related to carbon metabolism. Overall, our results suggest that adaptation of M. ovipneumoniae has involved evolution of carbon metabolism pathways and virulence mechanisms related to those pathways. The genes involved in these pathways, along with other genes identified as potentially involved in virulence in this study, are potential targets for future investigation into a possible genomic basis for the high variation observed in disease outcomes within and between wild and domestic host species.

Surgical Management of Iatrogenic Mercury Poisoning From Subcutaneous Injection Into the Arm.

BACKGROUND: Mercury, an element with threats of severe toxic insult to humans and no biological function, has a surprisingly extensive record of human exposure. Regardless of hesitancies toward its harmfulness, it has been historically identified with an almost supernatural power to provide protection from evil and sickness, give good fortune, lend aid in athletic undertakings, or even allow one to achieve immortality. Mercury poisoning is an iatrogenic disease even today as people attempt to achieve these effects through volitional injections into their body by practitioners. Although an uncommon practice in the United States, awareness of patient presentation after volitional injections of elemental mercury is necessary for appropriate treatment of these patients. We aim to increase awareness of the cultural practice of subcutaneous injections of mercury, as it is uncommonly seen in the United States, to contribute a broader understanding to the patient's medical presentation and describe an approach and the impact of medical and surgical intervention. METHODS: In this report, we describe a rare case of elemental mercury poisoning secondary to volitional subcutaneous injection to the arm. Initial management of care through chelation therapy and monitoring of renal and serum mercury levels in addition to symptoms of systemic spread was overseen by an internal medicine physician and poison control. Surgical intervention via full-thickness excision of the visible mercury to the right arm followed by local flap and skin grafting reconstruction was performed. CONCLUSIONS: Mercury poisoning from intentional subcutaneous administration is an uncommon patient presentation in the United States; however, knowledge of management of this rare condition is important for effective management of iatrogenic mercury toxicity.

Correction: Effects of structured exercise programmes on physiological and psychological outcomes in adults with inflammatory bowel disease (IBD): A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0278480.].

Implementation of an Enhanced Recovery After Surgery Protocol for Cranial Vault Remodeling Procedures.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been implemented across surgical disciplines, including cranial vault remodeling for craniosynostosis. The authors aim to describe the implementation of an ERAS protocol for cranial vault remodeling procedures performed for patients with craniosynostosis at a tertiary care hospital. DESCRIPTION: Institutional review board approval was received. All patients undergoing a cranial remodeling procedure for craniosynostosis at the authors' institution over a 10-year period were collected (n = 168). Patient and craniosynostosis demographics were collected as well as operative details. Primary outcome measures were intensive care unit length of stay (ICU LOS) and narcotic usage. Chi squared and independent t-tests were employed to determine significance. A significance value of 0.05 was utilized. RESULTS: During the time examined, there were 168 primary cranial vault remodeling procedures performed at the authors' institution - all of which were included in the analysis. Use of the ERAS protocol was associated with decreased initial 24-hour morphine equivalent usage (p < 0.01) and decreased total morphine equivalent usage (p < 0.01). Patients using the ERAS protocol experienced a shorter ICU LOS (p < 0.01), but the total hospital length of stay was unchanged. CONCLUSION: This study reiterates the benefit of developing and implementing an ERAS protocol for patients undergoing cranial vault remodeling procedures. The protocol resulted in an overall decreased ICU LOS and a decrease in narcotic use. This has implications for ways to maximize hospital reimbursement for these procedures, as well as potentially improve outcomes.

Effects of inspiratory muscle training on thoracoabdominal volume regulation in older adults: A randomised controlled trial.

OBJECTIVES: We investigated the effect of inspiratory muscle training (IMT) on inspiratory muscle strength, functional capacity and respiratory muscle kinematics during exercise in healthy older adults. METHODS: 24 adults were randomised into an IMT or SHAM-IMT group. Both groups performed 30 breaths, twice daily, for 8 weeks, at intensities of ∼50 % maximal inspiratory pressure (PImax; IMT) or <15 % PImax (SHAM-IMT). Measurements of PImax, breathing discomfort during a bout of IMT, six-minute walk distance, physical activity levels, and balance were assessed pre- and post-intervention. Respiratory muscle kinematics were assessed via optoelectronic plethysmography (OEP) during constant work rate cycling. RESULTS: PImax was significantly improved (by 20.0±11.9 cmH2O; p=0.001) in the IMT group only. Breathing discomfort ratings during IMT significantly decreased (from 3.5±0.9-1.7±0.8). Daily sedentary time was decreased (by 28.0±39.8 min; p=0.042), and reactive balance significantly improved (by 1.2±0.8; p<0.001) in the IMT group only. OEP measures showed a significantly greater contribution of the pulmonary and abdominal rib cage compartments to total tidal volume expansion post-IMT. CONCLUSIONS: IMT significantly improves inspiratory muscle strength and breathing discomfort in this population. IMT induces greater rib cage expansion and diaphragm descent during exercise, thereby suggesting a less restrictive effect on thoracic expansion and increased diaphragmatic power generation.

Ovine Herpesvirus 2 Glycoprotein B Complementation Restores Infectivity to a Bovine Herpesvirus 4 gB-Null Mutant.

Ovine herpesvirus 2 (OvHV-2) and bovine herpesvirus 4 (BoHV-4) are gamma herpesviruses that belong to the genera Macavirus and Rhadinovirus, respectively. As with all herpesviruses, both OvHV-2 and BoHV-4 express glycoprotein B (gB), which plays an essential role in the infection of host cells. In that context, it has been demonstrated that a BoHV-4 gB-null mutant is unable to infect host cells. In this study, we used homologous recombination to insert OvHV-2 ORF 8, encoding gB, into the BoHV-4 gB-null mutant genome, creating a chimeric BoHV-4 virus carrying and expressing OvHV-2 gB (BoHV-4∆gB/OvHV-2-gB) that was infectious and able to replicate in vitro. We then evaluated BoHV-4∆gB/OvHV-2-gB as a potential vaccine candidate for sheep-associated malignant catarrhal fever (SA-MCF), a fatal disease of ungulates caused by OvHV-2. Using rabbits as a laboratory model for MCF, we assessed the safety, immunogenicity, and efficacy of BoHV-4∆gB/OvHV-2-gB in an immunization/challenge trial. The results showed that while BoHV-4∆gB/OvHV-2-gB was safe and induced OvHV-2 gB-specific humoral immune responses, immunization conferred only 28.5% protection upon challenge with OvHV-2. Therefore, future studies should focus on alternative strategies to express OvHV-2 proteins to develop an effective vaccine against SA-MCF.

Trends in Demographic and Geographic Disparities in Stroke Mortality Among Older Adults in the United States.

BACKGROUND: Stroke is a leading cause of morbidity and mortality in the United States among older adults. However, the impact of demographic and geographic risk factors remains ambiguous. A clear understanding of these associations and updated trends in stroke mortality can influence health policies and interventions. METHODS: This study characterizes stroke mortality among older adults (age ≥55) in the US from January 1999 to December 2020, sourcing data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research. Segmented regression was used to analyze trends in crude mortality rate and age-adjusted mortality rate (AAMR) per 100,000 individuals stratified by stroke subcategory, sex, ethnicity, urbanization, and state. RESULTS: A total of 3,691,305 stroke deaths occurred in older adults in the US between 1999 and 2020 (AAMR = 233.3), with an overall decrease in AAMR during these years. The highest mortality rates were seen in nonspecified stroke (AAMR = 173.5), those 85 or older (crude mortality rate1276.7), men (AAMR = 239.2), non-Hispanic African American adults (AAMR = 319.0), and noncore populations (AAMR = 276.1). Stroke mortality decreased in all states from 1999 to 2019 with the greatest and least decreases seen in California (-61.9%) and Mississippi (-35.0%), respectively. The coronavirus pandemic pandemic saw increased stroke deaths in most groups. CONCLUSIONS: While there's a decline in stroke-related deaths among US older adults, outcome disparities remain across demographic and geographic sectors. The surge in stroke deaths during coronavirus pandemic reaffirms the need for policies that address these disparities.

Unsupervised machine learning models reveal predictive clinical markers of glioblastoma patient survival using white blood cell counts prior to initiating chemoradiation.

Background: Glioblastoma is a malignant brain tumor requiring careful clinical monitoring even after primary management. Personalized medicine has suggested the use of various molecular biomarkers as predictors of patient prognosis or factors utilized for clinical decision-making. However, the accessibility of such molecular testing poses a constraint for various institutes requiring identification of low-cost predictive biomarkers to ensure equitable care. Methods: We collected retrospective data from patients seen at Ohio State University, University of Mississippi, Barretos Cancer Hospital (Brazil), and FLENI (Argentina) who were managed for glioblastoma-amounting to 581 patient records documented using REDCap. Patients were evaluated using an unsupervised machine learning approach comprised of dimensionality reduction and eigenvector analysis to visualize the inter-relationship of collected clinical features. Results: We discovered that the serum white blood cell (WBC) count of a patient during baseline planning for treatment was predictive of overall survival with an over 6-month median survival difference between the upper and lower quartiles of WBC count. By utilizing an objective PD-L1 immunohistochemistry quantification algorithm, we were further able to identify an increase in PD-L1 expression in glioblastoma patients with high serum WBC counts. Conclusions: These findings suggest that in a subset of glioblastoma patients the incorporation of WBC count and PD-L1 expression in the brain tumor biopsy as simple biomarkers predicting glioblastoma patient survival. Moreover, machine learning models allow the distillation of complex clinical data sets to uncover novel and meaningful clinical relationships.

Understanding baseline levels of physiological stress tolerance from excessive exercise in a holobenthic octopus species, Octopus pallidus.

Cephalopods receive a great deal of attention due to their socioeconomically important fisheries and aquaculture industries as well their unique biological features. However, basic information about their physiological responses under stress conditions is lacking. This study investigated the impact of a simple stressor, exercise to exhaustion, on the activity levels of antioxidant enzymes and the concentrations of molecules involved in oxidative stress response in the pale octopus (Octopus pallidus). Eight biochemical assays were measured in the humoral (plasma) and cellular (hemocyte) components of O. pallidus haemolymph, the invertebrate analogue to vertebrate blood. Overall, exercise resulted in an increase in activity of plasma catalase (CAT) and glutathione-S-transferase (GST) and the decrease in activity of plasms glutathione reductase (GR). In the hemocytes, the exercise elicited a different response, with a reduction in the activity of superoxide dismutase (SOD), GR, and glutathione peroxidase (GPX) and a reduction in nitric oxide (NO) concentration. Malondialdehyde (MDA) activity was similar in the plasma and haemocytes in control and exercised treatments, indicating that exercise did not induce lipid peroxidation. These results provide an important baseline for understanding oxidative stress in octopus, with exercise to exhaustion serving as a simple stressor which will ultimately inform our ability to detect and understand physiological responses to more complex stressors.

A group concept mapping and ethnographic study of intensive care rehabilitation culture.

BACKGROUND: Early physical activity and physical rehabilitation are advocated in the critical care unit for patients recovering from critical illness. Despite this, there are still many factors associated with implementation of early physical rehabilitation into routine critical care and practice. One such factor that has been consistently identified is unit culture, yet there is little understanding of how or why the culture of a critical care unit impacts on implementation of early rehabilitation. AIM: To develop a detailed understanding of the cultural barriers and enablers to the promotion and implementation of physical activity and early mobilization in National Health Service (NHS) critical care units in the United Kingdom (UK). STUDY DESIGN: A mixed-methods, two-phase study incorporating online group concept mapping (GCM) and ethnography. GCM will be conducted to provide a multistakeholder co-authored conceptual framework of rehabilitation culture. Ethnographic observations and interviews will be conducted of culture and behaviours in relation to the implementation and promotion of early physical activity and rehabilitation in two NHS critical care units in the North East of England. RESULTS: The results of the Group Concept Mapping and ethnographic observations and interviews will be triangulated to develop a contextual framework of rehabilitation culture in critical care. RELEVANCE TO CLINICAL PRACTICE: This study will provide a detailed understanding of barriers and facilitators in relation to providing a positive rehabilitation culture in the critical care unit.

Consumer nutrition environment measurements for nutrient-dense food availability and food sustainability: a scoping review.

Consumer nutrition environments are defined as places in which consumers interact with the food they eat; these food choices can impact human and planetary health. Assessment measures for consumer nutrition environments are numerous, and vary widely on what, and how, they assess the food environment. The objective of this scoping review was to synthesize existing evidence on nutrition environment measurements and their capacity to assess nutrient-dense food access and food sustainability capacity. Eligibility criteria were developed to capture relevant peer-reviewed literature about auditing measures designed to assess nutrient-dense foods and food sustainability capacity in the consumer nutrition environment. A search strategy was conducted to collect articles published between January 1, 2002-June 4, 2022, using PubMed, Web of Science, Scopus, PsycINFO and the Cochrane library electronic databases. After screening 2457 manuscripts, 58 met inclusion criteria. Study aims, funding source(s), types of retailers assessed, assessment format and name, constructs measured, food categories measured, assessment of validity and/or reliability, and other relevant data were extracted from each manuscript. Results showed that most measures use checklists, surveys, questionnaires or similar methods to assess availability, quality, and price of select food items as assessment constructs. Most do not assess nutrient-dense food availability, and even fewer assess food sustainability. Development of comprehensive, reliable, and valid consumer nutrition environment measures that assess nutrient-dense food availability and food sustainability is important for research, planning, evaluation and advocacy aimed at improving consumer food environments for human and planetary health.

A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain.

The mammalian brain consists of millions to billions of cells that are organized into many cell types with specific spatial distribution patterns and structural and functional properties1-3. Here we report a comprehensive and high-resolution transcriptomic and spatial cell-type atlas for the whole adult mouse brain. The cell-type atlas was created by combining a single-cell RNA-sequencing (scRNA-seq) dataset of around 7 million cells profiled (approximately 4.0 million cells passing quality control), and a spatial transcriptomic dataset of approximately 4.3 million cells using multiplexed error-robust fluorescence in situ hybridization (MERFISH). The atlas is hierarchically organized into 4 nested levels of classification: 34 classes, 338 subclasses, 1,201 supertypes and 5,322 clusters. We present an online platform, Allen Brain Cell Atlas, to visualize the mouse whole-brain cell-type atlas along with the single-cell RNA-sequencing and MERFISH datasets. We systematically analysed the neuronal and non-neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type. The results reveal unique features of cell-type organization in different brain regions-in particular, a dichotomy between the dorsal and ventral parts of the brain. The dorsal part contains relatively fewer yet highly divergent neuronal types, whereas the ventral part contains more numerous neuronal types that are more closely related to each other. Our study also uncovered extraordinary diversity and heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types. Finally, we found that transcription factors are major determinants of cell-type classification and identified a combinatorial transcription factor code that defines cell types across all parts of the brain. The whole mouse brain transcriptomic and spatial cell-type atlas establishes a benchmark reference atlas and a foundational resource for integrative investigations of cellular and circuit function, development and evolution of the mammalian brain.

What is available to support pain management in Parkinson's: a scoping review protocol.

OBJECTIVE: A scoping review will be undertaken to examine and map the available evidence that has been produced in relation to pain management in Parkinson's, with a focus on behavioural interventions, resources and/or how professionals support people with Parkinson's self-management of pain. METHODS: This review will be based on the methodological framework given by Arksey and O'Malley's (2005), including enhancements by Levac et al., Peters et al. and the Joanna Briggs Institute. We will include studies from PubMed, SCOPUS, CINAHL, MEDLINE Web of Science, APA PsycINFO and ASSIA from January, 2010 onwards. Both quantitative and qualitative data will be analysed separately to identify the characteristics of support for pain management available, orientation of the approach and any identifiable behaviour change components and their outcomes. The COM-B behaviour change model and Theoretical Domains Framework will provide a theoretical framework for synthesising evidence in this review. CONCLUSION: This scoping review will help to explore studies focusing on the evidence supporting a range of interventions relating to the management of pain experienced by people living with Parkinson's. The focus will be on describing what is available to support self-management, identify what behaviour change components have been used and their effectiveness, identify barriers and enablers to pain management and explore gaps in current provision of pain management. This review will identify implications and priorities for the follow-up phases to the larger 'Pain in Parkinson's' Project which is designed to support clinicians and individuals living with Parkinson's.

Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex.

Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1. Subclass and subtype comparisons showed stronger transcriptomic differences in human L1 and were correlated with strong morphoelectric variability along dimensions distinct from mouse L1 variability. Accompanied by greater layer thickness and other cytoarchitecture changes, these findings suggest that L1 has diverged in evolution, reflecting the demands of regulating the expanded human neocortical circuit.

Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex.

Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was used to reliably target and analyze GABAergic neuron subclasses and individual transcriptomic types. This characterization elucidated transitions between PVALB and SST subclasses, revealed morphological heterogeneity within an abundant transcriptomic type, identified multiple spatially distinct types of the primate-specialized double bouquet cells (DBCs), and shed light on cellular differences between homologous mouse and human neocortical GABAergic neuron types. These results highlight the importance of multimodal phenotypic characterization for refinement of emerging transcriptomic cell type taxonomies and for understanding conserved and specialized cellular properties of human brain cell types.

Yoga and Multiple Sclerosis: Maintaining engagement in physical activity.

BACKGROUND: Physical activity is encouraged for people with Multiple Sclerosis. Yoga is a popular form of physical activity and is chosen by some people with Multiple Sclerosis. However, little is known about the impact of yoga for this population, alongside what influences ongoing engagement. AIM: The aim of this study is to qualitatively explore the impact of online home-based yoga on people with Multiple Sclerosis and to explore factors that influence engagement. METHODS: A qualitative study using semi-structured interviews and focus groups with people with Multiple Sclerosis and a yoga teacher. Thematic analysis was used to analyse the data. Ethical Approval was gained from Northumbria University. FINDINGS: Three overarching themes emerged from the analysis. 'Yoga as engagement in physical activity' captured the reasoning for participating in yoga and how this method of physical activity was an alternative to physical activity done prior to diagnosis. Frustration was apparent within this theme that some individuals were unable to engage in the range of physical activity that they wished to. 'Yoga is a personalised approach' demonstrated the flexibility and inclusivity of yoga, for individuals with varying symptoms to be able to engage with. Finally, 'yoga impacts individuals both physically and psychologically' captured the focus on the psychological impact of yoga, improving wellbeing and control. CONCLUSIONS: Yoga gives people with Multiple Sclerosis the feeling of control over their symptoms and a means to engage with meaningful physical activity. Prior involvement in physical activity influenced engagement in yoga and wanting to push themselves. There was reluctance among this group to engage with aerobic activity, which warrants future investigation and support from health and exercise professionals.

A guide to the BRAIN Initiative Cell Census Network data ecosystem.

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain with demonstration of prototype feasibility for human and nonhuman primate (NHP) brains. Here, we provide a guide to the cellular and spatial approaches employed by the BICCN, and to accessing and using these data and extensive resources, including the BRAIN Cell Data Center (BCDC), which serves to manage and integrate data across the ecosystem. We illustrate the power of the BICCN data ecosystem through vignettes highlighting several BICCN analysis and visualization tools. Finally, we present emerging standards that have been developed or adopted toward Findable, Accessible, Interoperable, and Reusable (FAIR) neuroscience. The combined BICCN ecosystem provides a comprehensive resource for the exploration and analysis of cell types in the brain.

Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human neocortex.

Rodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not been well investigated in human cortex, where there are major technical challenges in reliably obtaining healthy tissue, conducting multiple patch-clamp recordings on inhibitory cell types, and identifying those cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings, post-hoc fluorescent in situ hybridization (FISH), machine learning-based cell type classification and prospective GABAergic AAV-based labeling to investigate synaptic properties between pyramidal neurons and PVALB- vs. SST-positive interneurons. We find that there are robust molecular differences in synapse-associated genes between these neuron types, and that individual presynaptic pyramidal neurons evoke postsynaptic responses with heterogeneous synaptic dynamics in different postsynaptic cell types. Using molecular identification with FISH and classifiers based on transcriptomically identified PVALB neurons analyzed by Patch-seq, we find that PVALB neurons typically show depressing synaptic characteristics, whereas other interneuron types including SST-positive neurons show facilitating characteristics. Together, these data support the existence of target cell-specific synaptic properties in human cortex that are similar to rodent, thereby indicating evolutionary conservation of local circuit connectivity motifs from excitatory to inhibitory neurons and their synaptic dynamics.